The presence of micrometer-level restrictions leads to a decrease of diffusion coefficient with diffusion time. Here we investigate this effect in human white matter in vivo. We focus on a broad range of diffusion times, up to 600 ms, covering diffusion length scales up to about 30 microns. We perform stimulated echo diffusion tensor imaging on 5 healthy volunteers and observe a relatively weak time-dependence in diffusion transverse to major fiber tracts. Remarkably, we also find notable time-dependence in the longitudinal direction. Comparing models of diffusion in ordered, confined and disordered media, we argue that the time-dependence in both directions can arise due to structural disorder, such as axonal beads in the longitudinal direction, and the random packing geometry of fibers within a bundle in the transverse direction. These time-dependent effects extend beyond a simple picture of Gaussian compartments, and may lead to novel markers that are specific to neuronal fiber geometry at the micrometer scale.

There is a measurable time dependence of ADC in prostate cancer, which is dependent on the underlying tissue and Gleason score. Therefore, there may be an optimal selection of t for prediction of tumor grade using ADC. Controlling t should allow ADC to achieve greater reproducibility between different sites and vendors. Intentionally varying t enables targeted exploration of D(t), a previously overlooked biophysical phenomenon in the prostate. Its further microstructural understanding and modeling may lead to novel diffusion-derived biomarkers.

The time dependence of the diffusion coefficient is a hallmark of tissue complexity at the micrometer level. Here we demonstrate how biophysical modeling, combined with a specifically tailored diffusion MRI acquisition performing diffusion tensor imaging (DTI) for varying diffusion times, can be used to determine fiber size and membrane permeability of muscle fibers in vivo. We describe the random permeable barrier model (RPBM) and its assumptions, as well as the details of stimulated echo DTI acquisition, signal processing steps, and potential pitfalls. We illustrate the RPBM method on a few pilot examples involving human subjects (previously published as well as new), such as revealing myofiber size derived from RPBM increase after training in a calf muscle, and size decrease with atrophy in shoulder rotator cuff muscle. Finally, we comment on the potential clinical relevance of our results. Copyright © 2016 John Wiley & Sons, Ltd.

For many pathologies, early structural tissue changes occur at the cellular level, on the scale of micrometers or tens of micrometers. Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool used for medical diagnosis, but its clinical hardware is incapable of reaching the cellular length scale directly. In spite of this limitation, microscopic tissue changes in pathology can potentially be captured indirectly, from macroscopic imaging characteristics, by studying water diffusion. Here we focus on water diffusion and NMR relaxation in the human prostate, a highly heterogeneous organ at the cellular level. We present a physical picture of water diffusion and NMR relaxation in the prostate tissue, that is comprised of a densely-packed cellular compartment (composed of stroma and epithelium), and a luminal compartment with almost unrestricted water diffusion. Transverse NMR relaxation is used to identify fast and slow T2 components, corresponding to these tissue compartments, and to disentangle the luminal and cellular compartment contributions to the temporal evolution of the overall water diffusion coefficient. Diffusion in the luminal compartment falls into the short-time surface-to-volume (S/V) limit, indicating that only a small fraction of water molecules has time to encounter the luminal walls of healthy tissue; from the S/V ratio, the average lumen diameter averaged over three young healthy subjects is measured to be 217.7±188.7 μm. Conversely, the diffusion in the cellular compartment is highly restricted and anisotropic, consistent with the fibrous character of the stromal tissue. Diffusion transverse to these fibers is well described by the random permeable barrier model (RPBM), as confirmed by the dynamical exponent ϑ = 1/2 for approaching the long-time limit of diffusion, and the corresponding structural exponent p = −1 in histology. The RPBM-derived fiber diameter and membrane permeability were 19.8±8.1 μm and 0.044±0.045 μm/ms, respectively, in agreement with known values from tissue histology and membrane biophysics. Lastly, we revisited 38 prostate cancer cases from a recently published study, and found the same dynamical exponent ϑ = 1/2 of diffusion in tumors and benign regions. Our results suggest that a multi-parametric MRI acquisition combined with biophysical modeling may be a powerful non-invasive complement to prostate cancer grading, potentially foregoing biopsies.

To develop and evaluate a neural network-based method for Gibbs artifact and noise removal. Methods: A convolutional neural network (CNN) was designed for artifact removal in diffusion-weighted imaging data. Two implementations were considered: one for magnitude images and one for complex images. Both models were based on the same encoder-decoder structure and were trained by simulating MRI acquisitions on synthetic non-MRI images. Results: Both machine learning methods were able to mitigate artifacts in diffusionweighted images and diffusion parameter maps. The CNN for complex images was also able to reduce artifacts in partial Fourier acquisitions. Conclusions: The proposed CNNs extend the ability of artifact correction in diffusion MRI. The machine learning method described here can be applied on each imaging slice independently, allowing it to be used flexibly in clinical applications.